1. Field of the Invention
The present invention relates to a method of evaluating visceral fat accumulation, a visceral fat accumulation-evaluating apparatus, a visceral fat accumulation-evaluating method, a visceral fat accumulation-evaluating system, a visceral fat accumulation-evaluating program, and a recording medium, which utilize concentrations of amino acids in blood (plasma).
The present invention also relates to a method of searching for prophylactic/ameliorating substance for visceral fat accumulation, wherein a substance for preventing a visceral fat accumulation or ameliorating a visceral fat accumulation condition is searched.
2. Description of the Related Art
In recent years, along with an increase in the opportunities to take high-fat diet or a decrease in the opportunities for exercise, the problem of a visceral fat accumulation, which is one of the diagnostic criteria for metabolic syndrome, is rising as an issue. If the visceral fat level is high, even though the degree of hypertension, diabetes, hyperlipidemia or the like may be low, the risk of myocardial infarction or cerebral infarction drastically increases. Thus, it is thought that the visceral fat accumulation is causative of many lifestyle diseases. Therefore, the problem of how to reduce the risk of the visceral fat accumulation and to prevent the visceral fat accumulation is attracting attention as an urgent issue for healthcare insurance.
Since the visceral fat accumulation due to obesity causes hypertension, diabetes and hyperlipidemia, which in turn develop into arteriosclerosis, it is considered that the visceral fat accumulation constitutes a particularly important criterion among the diagnostic criteria for metabolic syndrome. It is also known that concomitantly with the visceral fat accumulation, hyperinsulinemia occurs, or the balance in the adipocytokine secreted from adipose tissues is disrupted.
At the 102nd annual meeting of the Japanese Society of Internal Medicine in April, 2005, the diagnostic criteria for metabolic syndrome in the Japanese population (see “Metabolic Syndrome Diagnostic Criteria Review Committee, Journal of the Japanese Society of Internal medicine, 94, 794, 2005.”) were established by eight related academic societies, including the Japanese Society of Internal Medicine (eight academic societies including Japan Society for the Study of Obesity, Japan Atherosclerosis Society, Japan Diabetes Society, the Japanese Society of Hypertension, the Japanese Circulation Society, Japanese Society of Nephrology, the Japanese Society on Thrombosis and Hemostasis, and the Japanese Society of Internal Medicine). At the annual meeting, the diagnostic criterion for visceral fat accumulation was determined to be a visceral fat area of 100 cm2 or more, and the waist circumference (abdominal circumference) corresponding to this area was determined to be 85 cm or more for men and 90 cm or more for women. If the criterion for visceral fat accumulation is satisfied, and two or more items among the three items listed below are met, the condition is determined as metabolic syndrome. Furthermore, if only one item among the following three items is met, the condition is regarded as premetabolic syndrome.
1. The systolic blood pressure is 130 mmHg or higher, or the diastolic blood pressure is 85 mmHg or higher.
2. The fasting blood glucose level is 110 mg/dL or higher.
3. The triglyceride level is 150 mg/mL or higher, or the HDL-cholesterol level is lower than 40 mg/dL.
According to the “National Health and Nutrition Examination Survey, 2004” reported by the Ministry of Health, Labour and Welfare in May, 2006, the population of patients at age 40 to 74 with visceral fat syndrome or pre-visceral fat syndrome reached about 20 million, which corresponds to one-third of the entire population of this generation. The proportion of those who were strongly suspected was 25.7% for male and 10.0% for female, and the proportion of those who were considered to have pre-visceral fat syndrome was 26.0% for male and 9.6% for female.
Since the visceral fat accumulation is causative of lifestyle diseases, and also the proportion of those patients with visceral fat syndrome is high, it may be said to be an important task to measure the visceral fat accumulation inexpensively, conveniently and quickly, and to suggest guidelines for amelioration from the findings on the level of metabolism. The diagnosis of the visceral fat accumulation involves the use of the abdominal visceral fat area or the abdominal circumference. However, each of these indicators has problems, such as that the measurement of visceral fat area frequently requires computer tomography (CT) and demand cost, time and labor, while the measurement of the abdominal circumference is subject to change in the value depending on the measurer and is associated with a possibility that subcutaneous fat accumulation is confused with the visceral fat accumulation, bringing about an overlook of hidden obesity.
Meanwhile, amino acid metabolism is affected in peripheral tissues, by the insulin resistance derived from the visceral fat accumulation. Prior technology literatures report the results of the researches on the amino acid metabolism in obesity patients or diabetic rats, in which changes are seen in the blood plasma levels of amino acids related to obesity or insulin resistance attributed thereto (see “Felig, P., Marliss, E., et al., New Engl. J. Med., 281, 881 (1969).” or “Felig, P., Marliss, E., et al., Diabetes, 19, 727 (1970).”).
If amino acids that specifically vary in the peripheral blood level or the like in the group of patients with the visceral fat accumulation, were discovered, and index formulae using the concentration parameters of the varying amino acids could be established, the index formulae would be able to be widely applied as a convenient and sensitive detection method that reflects the background metabolic changes in the visceral fat accumulation. In regard to the method of diagnosing a disease state using blood amino acids, the indices described in WO 2004/052191 and WO 2006/098192 are known. However, in WO 2004/052191, the object of clinical diagnosis is an index intended to discriminate between hepatitis C patients and hepatitis-free subjects, while in WO 2006/098192, the object of clinical diagnosis is an index intended to discriminate between Crohn's disease patients and healthy subjects, and to discriminate between ulcerative colitis patients and healthy subjects.
However, there is a problem that there are reports on changes of amino acids in obesity or diabetes, and there is no report on a metabolic pattern of amino acids in peripheral blood in a visceral fat accumulation condition. Specifically, there is also a problem that there is no report on application to a diagnostic method for a discrimination between 2 groups of a visceral fat accumulation group and a visceral fat accumulation-free group or for an evaluation of a visceral fat area state.
There is a problem that technology of diagnosing the visceral fat accumulation condition with a plurality of amino acids as explanatory variables is not developed and not practically used.